Fluoroquinolone-Resistant and Extended-Spectrum β ... a presumptive diagnosis of acute...
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1594 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 22, No. 9, September 2016
Fluoroquinolone-Resistant and Extended-Spectrum β-Lactamase–
Producing Escherichia coli Infections in Patients with
Pyelonephritis, United States1 David A. Talan, Sukhjit S. Takhar, Anusha Krishnadasan, Fredrick M. Abrahamian,
William R. Mower, Gregory J. Moran; EMERGEncy ID Net Study Group
This activity has been planned and implemented through the joint providership of Medscape, LLC and Emerging Infectious Diseases. Medscape, LLC is accredited by the American Nurses Credentialing Center (ANCC), the Accreditation Council for Pharmacy Education (ACPE) and the Accreditation Council for Continuing Medical Education (ACCME), to provide continuing education for the healthcare team.
Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s)™ . Physicians should claim only the credit commensurate with the extent of their participation in the activity.
All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at http://www.medscape.org/journal/eid; and (4) view/print certificate. For CME questions, see page 1701.
Release date: August 12, 2016; Expiration date: August 12, 2017
Learning Objectives Upon completion of this activity, participants will be able to:
• Assess recommendations regarding the treatment of pyelonephritis • Distinguish the rates of fluoroquinolone resistance and extended-spectrum β-lactamase (ESBL) production among patients with pyelonephritis in the current study • Evaluate risk factors for fluoroquinolone resistance in the current study • Evaluate risk factors for ESBL production in the current study
CME Editor Rhonda Ray, PhD, Copyeditor, Emerging Infectious Diseases. Disclosure: Rhonda Ray, PhD, has disclosed no relevant financial relationships.
CME Author Charles P. Vega, MD, Clinical Professor of Family Medicine, University of California, Irvine. Disclosure: Charles P. Vega, MD, has disclosed the following financial relationships: served as an advisor or consultant for Allergan, Inc.; McNeil Consumer Healthcare; served as a speaker or a member of a speakers bureau for Shire Pharmaceuticals.
Authors Disclosures: David A. Talan, MD, has disclosed the following relevant financial relationships: served as an advisor or consultant for Allergan, Inc.; Cempra; served as a speaker or a member of a speakers bureau for Allergan, Inc.; Merck; received grants for clinical research from Merck. Sukhjit S. Takhar, MD; Anusha Krishnadasan, PhD; and William R. Mower, MD, PhD, have disclosed no relevant financial relationships. Fredrick M. Abrahamian, DO, has disclosed the following relevant financial relationships: served as an advisor or consultant for Grifols; Cempra; Summitt Therapeutics; Tetraphase Pharmaceutics; Janssen; Seqirus; served as a speaker or a member of a speakers bureau for Merck; Actavis; Medicines Company; received grants for clinical research from Merck; Cempra; owns stock, stock options, or bonds from Gilead. Gregory J. Moran, MD, has disclosed the following relevant financial relationships: received grants for clinical research from Cempra; Allergan.
1Preliminary results of this research were presented at the 2014 IDWeek Meeting, Philadelphia, PA, USA, October 8–12, 2014.
E. coli Infections in Patients with Pyelonephritis
For 2013–2014, we prospectively identified US adults with flank pain, temperature >38.0°C, and a diagnosis of acute py- elonephritis, confirmed by culture. Cultures from 453 (86.9%) of 521 patients grew Escherichia coli. Among E. coli isolates from 272 patients with uncomplicated pyelonephritis and 181 with complicated pyelonephritis, prevalence of fluoroquinolone resistance across study sites was 6.3% (range by site 0.0%– 23.1%) and 19.9% (0.0%–50.0%), respectively; prevalence of extended-spectrum β-lactamase (ESBL) production was 2.6% (0.0%–8.3%) and 12.2% (0.0%–17.2%), respectively. Ten (34.5%) of 29 patients with ESBL infection reported no exposure to antimicrobial drugs, healthcare, or travel. Of the 29 patients with ESBL infection and 53 with fluoroquinolone- resistant infection, 22 (75.9%) and 24 (45.3%), respectively, were initially treated with in vitro inactive antimicrobial drugs. Prevalence of fluoroquinolone resistance exceeds treatment guideline thresholds for alternative antimicrobial drug strate- gies, and community-acquired ESBL-producing E. coli infec- tion has emerged in some US communities.
Escherichia coli, the predominant cause of community-acquired urinary tract infection (UTI) worldwide, is in- creasingly resistant to available antimicrobial drugs. In the United States, in vitro resistance of E. coli to trimethoprim/ sulfamethoxazole (TMP/SMX) became prevalent in the 1990s (1). Over the past decade, fluoroquinolone resistance rates have increased to >10% in some surveys (2,3).
In many parts of the world, E. coli fluoroquinolone re- sistance rates are >20% among patients with community- acquired uncomplicated UTI and >50% among patients with complicated infections (4). In addition, infections re- sulting from extended-spectrum β-lactamase (ESBL)–pro- ducing E. coli and other Enterobacteriaceae are becoming increasingly common in these same areas and are associ- ated with sequence type (ST) 131, a globally disseminated, multidrug-resistant clone that frequently produces CTX- M-15 ESBL. These E. coli isolates are generally resistant to cephalosporins and often to other antimicrobial drug classes. In North America, ESBL-producing E. coli infec- tions have occurred predominantly in patients with health- care exposure and have not become prevalent as a cause of community-acquired infections (5–8).
The 2010 international treatment guidelines of the Infec- tious Disease Society of America (IDSA) recommend for acute
uncomplicated pyelonephritis a fluoroquinolone and an initial dose of an agent from another antimicrobial drug class (e.g., ceftriaxone or gentamicin) if the fluoroquinolone resistance rate is >10% (9). For uncomplicated cystitis, the guidelines discourage use of an antimicrobial drug if its resistance rate is >20%. The guidelines do not address a scenario in which ESBL-producing uropathogens have become prevalent among patients with community-acquired infections. Use of antimi- crobial drugs for which the uropathogen shows in vitro resis- tance has been associated with substantially reduced response rates (1,10,11), which can lead to serious consequences, par- ticularly for patients with pyelonephritis. Given rapid changes in global resistance patterns and a lack of recent active and prospective surveillance of community-acquired UTI in the United States, the extent to which the prevalence of fluoroqui- nolone resistance has increased and multidrug-resistant ESBL- producing strains have emerged in the community is unknown.
We sought to determine the prevalence of E. coli an- timicrobial resistance among patients with acute pyelo- nephritis who sought care at a US emergency department (ED)–based sentinel research network. We focused on flu- oroquinolone-resistant and ESBL-producing isolates from these patients and examined risk factors for antimicrobial drug resistance.
Participants We recruited adults seeking care in EMERGEncy ID NET, a network of 10 university-affiliated urban US EDs (12). All 10 study sites (online Technical Appendix, http://ww- wnc.cdc.gov/EID/article/22/9/16-0148-Techapp1.pdf) pro- vided institutional review board approval.
We enrolled patients >18 years of age who sought care during July 2013–December 2014 and had flank pain or costovertebral tenderness; temperature >38.0°C (100.4°F) measured by any method (i.e., oral, rectal, or axillary); and a presumptive diagnosis of acute pyelonephritis (i.e., pa- tient received treatment for this infection during ED visit or was prescribed treatment at discharge). All sites conducted an audit to compare characteristics of enrolled and nonen- rolled eligible patients to estimate case-finding sensitivity and detect enrollment biases (online Technical Appendix).
Design and Measurements We conducted a cross-sectional study by using a convenience sample of prospectively identified patients. ED physicians or study coordinators who used standardized forms at the time of care collected the following: demographic characteristics (i.e., age, sex, race, ethnicity); symptom duration; urinary tract abnormalities; UTI within the previous year; concurrent and immunocompromising conditions; antimicrobial drug use within the previous 2 and 60 days; a fluoroquinolone- or
Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 22, No. 9, September 2016 1595
Author affiliations: David Geffen School of Medicine at the University of California, Los Angeles (UCLA), Los Angeles, California, USA (D.A. Talan, A. Krishnadasan, F.M. Abrahamian, W.R. Mower, G.J. Moran); Olive View–UCLA Medical Center, Los Angeles (D.A. Talan, A. Krishnadasan, F.M. Abrahamian, G.J. Moran); Brigham and Women’s Hospital, Boston, Massachusetts, USA (S.S. Takhar); Harvard Medical School, Boston (S.S. Takhar); Ronald Reagan Medical Center, Los Angeles (W.R. Mower)